Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website http://www.gastrores.org

Original Article

Volume 3, Number 6, December 2010, pages 262-271

Clinical Benefits of Biochemical Markers of Fibrosis in Egyptian Children With Chronic Liver Diseases

Figure 1. Box-and-whiskers plot for serum biochemical markers. The top and bottom of each box are the 25th and 75th centiles. The line through the box is the median and the error bars are the maximum and minimum. The horizontal bar represents the significance between the designated groups. * P ≤ 0.05 and ** P ≤ 0.01.

Figure 2. Receiver-operator characteristic (ROC) curves of serum biochemical markers for prediction of significant fibrosis (Ishak score > 2). Data were analyzed considering patients with liver biopsy in the chronic hepatitis group. Among them collagen IV was the most sensitive and specific.

**Table 1.** Demographic, Clinical and Laboratory Characteristics of the Studied Patients
Characteristics	HBV (n = 12)	HCV (n = 29)	Bilharziasis (n = 9)	P-value
Quantitative data are expressed as mean ± SEM and qualitative data as number and %. Significance was tested using non-parametric Kruskal-Wallis test or Chi-square test. P ≤ 0.05, *P ≤ 0.01
Age (years)	Patients	10.75 ± 1.04	11.54 ± 0.63	11.89 ± 1.1	0.206
	Controls 10.5 ± 0.46
Male n (%)	Patients	10 (83.3%)	22 (75.9%)	9 (100%)	0.355
	Controls 22 (73.3%)
Hematemesis n (%)	1 (8.3%)	4 (13.8%)	3 (33.3%)	0.267
Epistaxis n (%)	1 (8.3%)	4 (13.8%)	2 (22.2%)	0.662
Hepatomegaly n (%)	2 (16.6%)	8 (27.6%)	2 (22.2%)	0.751
Splenomegaly n (%)	7 (58.3%)	19 (56.5%)	8 (88.8%)	0.301
Ascites n (%)	2 (16.6%)	4 (13.8%)	3 (33.3%)	0.506
Hb (g/dl)	10.5 ± 0.42	10.89 ± 0.34	11.18 ± 0.39	0.659
WBCs (x 10³/mm³)	6.38 ± 0.95	7.2 ± 0.49	7.04 ± 0.67	0.624
Platelets (x 10³/mm³)	135.4 ± 17.3	161.9 ± 14.1	196.7 ± 17.03	0.64
TB (mg/dl)	1.83 ± 0.22	1.32 ± 0.14	0.95 ± 0.16	0.026*
ALT (U/L)	72.58 ± 12.41	107.37 ± 28.1	30.67 ± 3.21	0.03*
AST (U/L)	71.17 ± 10.76	120.07 ± 21.78	38.56 ± 6.09	0.002**
Albumin (g/dl)	3.49 ± 0.19	3.57 ± 0.11	3.8 ± 0.1	0.35
Alkaline phosphatase (U/L)	214.33 ± 41.18	165.19 ± 28.86	80.33 ± 12.42	0.02*
GGT (U/L)	54.33 ± 15.98	59.87 ± 11.06	38.78 ± 9.64	0.61
PC (%)	69.42 ± 6.03	65.61 ± 2.46	75.67 ± 4.1	0.163

Table 1. Demographic, Clinical and Laboratory Characteristics of the Studied Patients

Characteristics

HBV (n = 12)

HCV (n = 29)

Bilharziasis (n = 9)

P-value

Quantitative data are expressed as mean ± SEM and qualitative data as number and %. Significance was tested using non-parametric Kruskal-Wallis test or Chi-square test. *P ≤ 0.05, **P ≤ 0.01

Age (years)

Patients

10.75 ± 1.04

11.54 ± 0.63

11.89 ± 1.1

0.206

Controls 10.5 ± 0.46

Male n (%)

Patients

10 (83.3%)

22 (75.9%)

9 (100%)

0.355

Controls 22 (73.3%)

Hematemesis n (%)

1 (8.3%)

4 (13.8%)

3 (33.3%)

0.267

Epistaxis n (%)

1 (8.3%)

4 (13.8%)

2 (22.2%)

0.662

Hepatomegaly n (%)

2 (16.6%)

8 (27.6%)

2 (22.2%)

0.751

Splenomegaly n (%)

7 (58.3%)

19 (56.5%)

8 (88.8%)

0.301

Ascites n (%)

2 (16.6%)

4 (13.8%)

3 (33.3%)

0.506

Hb (g/dl)

10.5 ± 0.42

10.89 ± 0.34

11.18 ± 0.39

0.659

WBCs (x 10³/mm³)

6.38 ± 0.95

7.2 ± 0.49

7.04 ± 0.67

0.624

Platelets (x 10³/mm³)

135.4 ± 17.3

161.9 ± 14.1

196.7 ± 17.03

0.64

TB (mg/dl)

1.83 ± 0.22

1.32 ± 0.14

0.95 ± 0.16

0.026*

ALT (U/L)

72.58 ± 12.41

107.37 ± 28.1

30.67 ± 3.21

0.03*

AST (U/L)

71.17 ± 10.76

120.07 ± 21.78

38.56 ± 6.09

0.002**

Albumin (g/dl)

3.49 ± 0.19

3.57 ± 0.11

3.8 ± 0.1

0.35

Alkaline phosphatase (U/L)

214.33 ± 41.18

165.19 ± 28.86

80.33 ± 12.42

0.02*

GGT (U/L)

54.33 ± 15.98

59.87 ± 11.06

38.78 ± 9.64

0.61

PC (%)

69.42 ± 6.03

65.61 ± 2.46

75.67 ± 4.1

0.163

**Table 2.** Serum Levels of Biochemical Markers in the Studied Groups
Marker	HBV n = 12	HCV n = 29	Bilharziasis n = 9	All Patients n = 50	Controls n = 30	P-valuea	P-valueb
^aSignificance was tested between all patients (n = 50) versus controls (n = 30) using Mann-Whitney test.
^bSignificance was tested among individual etiological (HBV, HCV and Bilharziasis) groups and controls using Kruskal-Wallis test.
** P < 0.01. Values are expressed as mean ± standard error of mean (SEM).
TGF-β1 (ng/ml)	61.7 ± 4.9	68.7 ± 2.6	65.5 ± 5.29	66.504 ± 2.14	50.9 ± 2.2	0.000**	0.000**
EGF-R (ng/ml)	0.904 ± 0.1	0.929 ± 0.1	1.2 ± 0. 19	0.97 ± 0.07	0.88 ± 0.05	0.315	0.699
Collagen IV (ng/ml)	211.1 ± 19.4	224.9 ± 14.3	226.1 ± 29.5	221.8 ± 10.7	85.6 ± 3.6	0.000**	0.000**
Laminin (ng/ml)	57.0 ± 4.8	68.9 ± 2.5	57.5 ± 6.6	64.05 ± 2.3	45.5 ± 2.4	0.000**	0.000**
MMP-2 (ng/ml)	849.3 ± 31.3	787.6 ± 33.6	762.2 ± 79.8	797.87 ± 25.18	653.4 ± 18.3	0.000**	0.000**

Table 2. Serum Levels of Biochemical Markers in the Studied Groups

Marker

HBV
n = 12

HCV
n = 29

Bilharziasis
n = 9

All Patients
n = 50

Controls
n = 30

P-valuea

P-valueb

^aSignificance was tested between all patients (n = 50) versus controls (n = 30) using Mann-Whitney test.

^bSignificance was tested among individual etiological (HBV, HCV and Bilharziasis) groups and controls using Kruskal-Wallis test.

** P < 0.01. Values are expressed as mean ± standard error of mean (SEM).

TGF-β1 (ng/ml)

61.7 ± 4.9

68.7 ± 2.6

65.5 ± 5.29

66.504 ± 2.14

50.9 ± 2.2

0.000**

EGF-R (ng/ml)

0.904 ± 0.1

0.929 ± 0.1

1.2 ± 0. 19

0.97 ± 0.07

0.88 ± 0.05

0.315

0.699

Collagen IV (ng/ml)

211.1 ± 19.4

224.9 ± 14.3

226.1 ± 29.5

221.8 ± 10.7

85.6 ± 3.6

0.000**

Laminin (ng/ml)

57.0 ± 4.8

68.9 ± 2.5

57.5 ± 6.6

64.05 ± 2.3

45.5 ± 2.4

0.000**

MMP-2 (ng/ml)

849.3 ± 31.3

787.6 ± 33.6

762.2 ± 79.8

797.87 ± 25.18

653.4 ± 18.3

0.000**

**Table 3.** Correlation Analysis of Biochemical Markers With Age and Laboratory Parameters in All the Patients (n = 50) and With HAI and Stage of Fibrosis in Chronic Hepatitis B and C Patients Only (n = 19)
Variable	TGF-β1	EGFR	Collage IV	Laminin	MMP-2
r = correlation coefficient, P ≤ 0.05, *P ≤ 0.01
EGFR	r	-0.25
	P	0.079
Collage IV	r	0.126	-0.156
	P	0.382	0.28
Laminin	r	0.024	0.034	0.205
	P	0.867	0.817	0.153
MMP-2	r	0.116	-0.030	-0.018	0.048
	P	0.423	0.838	0.899	0.739
Age	r	0.02	-0.122	0.202	0.044	0.103
	P	0.892	0.397	0.159	0.761	0.475
PLT	r	0.29	0.147	0.081	0.196	0.159
	P	0.041*	0.308	0.574	0.172	0.27
TBIL	r	-0.063	0.109	-0.053	0.093	0.068
	P	0.663	0.451	0.716	0.52	0.637
ALT	r	-0.027	-0.194	0.056	0.187	0.021
	P	0.854	0.178	0.701	0.193	0.886
AST	r	-0.083	-0.172	0.014	0.186	-0.125
	P	0.568	0.232	0.924	0.196	0.386
Albumin	r	0.155	0.017	0.099	-0.058	0.073
	P	0.283	0.906	0.495	0.687	0.616
ALP	r	0.047	-0.213	-0.066	0.033	0.236
	P	0.746	0.137	0.648	0.817	0.099
GGT	r	-0.06	0.011	0.123	0.104	0.075
	P	0.68	0.941	0.395	0.474	0.607
P.C	r	0.045	0.103	0.042	-0.016	0.11
	P	0.757	0.476	0.774	0.912	0.448
HAI	r	-0.226	0.117	0.138	0.636	0.072
	P	0.351	0.635	0.573	0.003**	0.769
Fibrosis stage	r	-0.196	0.005	-0.026	-0.083	-0.307
	P	0.421	0.985	0.915	0.734	0.201

Table 3. Correlation Analysis of Biochemical Markers With Age and Laboratory Parameters in All the Patients (n = 50) and With HAI and Stage of Fibrosis in Chronic Hepatitis B and C Patients Only (n = 19)

Variable

TGF-β1

EGFR

Collage IV

Laminin

MMP-2

r = correlation coefficient, *P ≤ 0.05, **P ≤ 0.01

EGFR

-0.25

0.079

Collage IV

0.126

-0.156

0.382

0.28

Laminin

0.024

0.034

0.205

0.867

0.817

0.153

MMP-2

0.116

-0.030

-0.018

0.048

0.423

0.838

0.899

0.739

Age

0.02

-0.122

0.202

0.044

0.103

0.892

0.397

0.159

0.761

0.475

PLT

0.29

0.147

0.081

0.196

0.159

0.041*

0.308

0.574

0.172

0.27

TBIL

-0.063

0.109

-0.053

0.093

0.068

0.663

0.451

0.716

0.52

0.637

ALT

-0.027

-0.194

0.056

0.187

0.021

0.854

0.178

0.701

0.193

0.886

AST

-0.083

-0.172

0.014

0.186

-0.125

0.568

0.232

0.924

0.196

0.386

Albumin

0.155

0.017

0.099

-0.058

0.073

0.283

0.906

0.495

0.687

0.616

ALP

0.047

-0.213

-0.066

0.033

0.236

0.746

0.137

0.648

0.817

0.099

GGT

-0.06

0.011

0.123

0.104

0.075

0.68

0.941

0.395

0.474

0.607

P.C

0.045

0.103

0.042

-0.016

0.11

0.757

0.476

0.774

0.912

0.448

HAI

-0.226

0.117

0.138

0.636

0.072

0.351

0.635

0.573

0.003**

0.769

Fibrosis stage

-0.196

0.005

-0.026

-0.083

-0.307

0.421

0.985

0.915

0.734

0.201

**Table 4.** Diagnostic Performance of Serum Biochemical Markers in Predicting Significant Fibrosis and Cirrhosis in Chronic Hepatitis B and C Patients
Marker	AUROC	P-value	Cut-off	Sensitivity	Specificity	PPV	NPV
P ≤ 0.05, *P ≤ 0.01
Significant Fibrosis (Ishak score > 2)
TGF-β1	0.74	0.01**	54.8	78.6	71.4	73.3	76.9
Collagen IV	0.94	0.000**	132.5	92.9	91.4	91.5	92.8
Laminin	0.82	0.001**	60.9	71.4	77.1	75.7	72.9
MMP-2	0.77	0.004**	742	85.7	71.4	74.9	83.3
Cirrhosis (Ishak score 6)
TGF-β1	0.7	0.089	57.5	85.7	66.6	72	82.3
Collagen IV	0.85	0.003**	147.5	85.7	78.6	80	85.1
Laminin	0.76	0.031*	63.7	71.4	81	78.9	73.9
MMP-2	0.68	0.126	747	85.7	64.3	70	81.8

Table 4. Diagnostic Performance of Serum Biochemical Markers in Predicting Significant Fibrosis and Cirrhosis in Chronic Hepatitis B and C Patients

Marker

AUROC

P-value

Cut-off

Sensitivity

Specificity

PPV

NPV

*P ≤ 0.05, **P ≤ 0.01

Significant Fibrosis (Ishak score > 2)

TGF-β1

0.74

0.01**

54.8

78.6

71.4

73.3

76.9

Collagen IV

0.94

0.000**

132.5

92.9

91.4

91.5

92.8

Laminin

0.82

0.001**

60.9

71.4

77.1

75.7

72.9

MMP-2

0.77

0.004**

742

85.7

71.4

74.9

83.3

Cirrhosis (Ishak score 6)

TGF-β1

0.7

0.089

57.5

85.7

66.6

82.3

Collagen IV

0.85

0.003**

147.5

85.7

78.6

85.1

Laminin

0.76

0.031*

63.7

71.4

78.9

73.9

MMP-2

0.68

0.126

747

85.7

64.3

81.8